The effect of elevated dopamine levels on behaviour in young adult rats after neonatal administration of N-acetylaspartylglutamate

Abstract

Neurodevelopmental models of schizophrenia are based on evidence that schizophrenia arise from abnormal brain development. Primary factors which can produce abnormal brain development are excitotoxic lesions.

In our experimental model we tested the effect of N-acetylaspartylglutamate (NAAG) in etiology of schizophrenia. We chose the dipeptide because of the evidence of increased NAAG level in hippocampus and prefrontal cortex in patients with schizophrenia.

We applied intracerebroventricular infusion (ICV) NAAG at 12. postnatal day (PD). Following the NAAG infusion, the extent and localization of lesions was observed.

Furthermore, deficit in social behavior and a change in exploratory behavior were observed after the application of dopamine uptake inhibitor (GBR 12909). Neonatal infusion of NAAG produced acute neurodegeneration of dorsal hippocampus, dorsal part of rostral thalamus and retrosplenial and cingular cortex.

Despite of large neurodegeneration, deficit in social behavior was not change (on day 10 after NAAG infusion). Administration of GBR 12909 resulted in increased exploratory behavior of rat in open field.

Our results indicate that NAAG has secondary role in the patophysiology of schizophrenia.